Association of obesity and its genetic predisposition with the risk of severe COVID-19: Analysis of population-based cohort data

Objective: We aimed to examine the associations of obesity-related traits (body mass index [BMI], central obesity) and their genetic predisposition with the risk of developing severe COVID-19 in a population-based data. Research design and methods: We analyzed data from 489,769 adults enrolled in the UK Biobank-a population-based cohort study. The exposures of interest are BMI categories and central obesity (e.g., larger waist circumference). Using genome-wide genotyping data, we also computed polygenic risk scores (PRSs) that represent an individual's overall genetic risk for each obesity trait. The outcome was severe COVID-19, defined by hospitalization for laboratory-confirmed COVID-19. Results: Of 489,769 individuals, 33% were normal weight (BMI, 18.5-24.9 kg/m(2)), 43% overweight (25.0-29.9 kg/ m(2)), and 24% obese (>= 30.0 kg/m(2)). The UK Biobank identified 641 patients with severe COVID-19. Compared to adults with normal weight, those with a higher BMI had a dose-response increases in the risk of severe COVID-19, with the following adjusted ORs: for 25.0-29.9 kg/m(2), 1.40 (95%0 1.14-1.73; P = 0.002): for 30.0-34.9 kg/m(2), 1.73 (95%CI 1.36-2.20; P < 0.001): for 35.0-39.9 kg/m(2), 2.82 (95%CI 2.08-3.83: P < 0.001): and for >= 40.0 kg/m(2), 3.30 (95%CI 2.17-5.03; P < 0.001). Likewise, central obesity was associated with significantly higher risk of severe COVID-19 (P < 0.001). Furthermore, larger PRS for BMI was associated with higher risk of outcome (adjusted OR per BMI PRS Z-score 1.14, 95%CI 1.05-124: P = 0.004). Conclusions: In this large population-based cohort, individuals with more-severe obesity, central obesity, or genetic predisposition for obesity are at higher risk of developing severe-COVID-19. (C) 2020 Elsevier Inc. All rights reserved.